Dr. Eric Winer on Aromatase Inhibitors (SABCS 2009)

LizM

Posting Dr. Winer's comments in the alternative forum is misleading as I just read his comments and he is clearly comparing the results of different regiments of hormone therapy and saying that the survival stats are comparable with Tamoxifen and the AI and a combination; however, he IS NOT saying anything about no hormone therapy at all.  Please don't be mislead by some of the posters in this thread.  I am a natural girl too but I believe in complimentary medicine in other words, use everything modern mediciine can provide to treat the disease and follow it up with organic diet, vitamins, supplements, excercise, etc.

Lowrider54

Oh dear...this is back again - Jane...you and I have been through this - while we have agreed to disagree on this topic - statistics and studies and 'facts' can be altered, slanted and quite frequently, 'parceled out' to make a point 'appear' valid. 

I had no side effects with Tamoxifin.  Sadly, I was in a high risk category for developing cervical/ovarian cancer and it was stopped at 2 1/2 years so I do not know what benefit it was - other than, I had 10 1/2 cancer-free years. 

When dx'd with distant mets to the spine, the first line of treatment was Arimidex - moved to Faslodex (another anti-hormonal) and just last week, I have acheived 'STABLE'.  16 months and 6 days following my dx with distant mets to the spine.  Not bad.  I have now been living wth cancer in my life for 13 years.  I agree with LizM - I use the traditional treatments and then to counter the se's - I use natural stuff and have changed my eating habits - the elimination of gluten in my diet totally rid me of joint pain - a common se of the antihormonals. 

The study referenced here only compares the effectiveness of Tamoxifin vs Arimidex - they are equally effective in preventing a recurrence - local and/or distant - typically, Tamoxifin is used pre and peri menopausal and Arimidex is used post menopausal but either can be used at either time - the se's can be more severe from Arimidex in some while Tamoxifin has its own set of risks. 

Do your homework and make an informed decision - the anti-hormonal therapy works to prevent a recurrence - nothing is 100% in the bc world and there are no guarentees except one - ignoring it will never make it go away.  All sorts of ways to manage the se's - rather that than be dealing with mets later. 

Thanks otter for the transcript...while he may be dissappointed by the results - the little tiny white pill works on mets quite nicely - it resolved all but one of my spinal lesions but we shifted to the Faslodex and it hit that one but didn't show too much promise until I got the new approved double dose and within 4 months, I am stable. 

Pardon the interuption on the Alternative Gals...I send folks over to you all the time - in fact, I find some of your suggestions very helpful.  I have elected the more traditional route with complementary natural stuff. 

Thanks for reading...Hugs...LowRider

otter

I am often (usually?) one of the skeptics, but I'm always interested to see what the regulars on the Alternatives forum have to say about aromatase inhibitors and estrogen suppression. 

In reference to LizM's concerns, I was glad Yazmin provided the link to Dr. Winer's remarks.  Yazmin has been trying to put that link here for a long time, but I haven't been able to download the video and/or get it to run until this time.  Eric Winer is a nationally (internationally) known, highly respected oncologist.  As Jane noted in one of her posts, Dr. Winer ranks pretty high up on that fairly short list of experts in the subject of ER+ tumors.  So, I really did want to hear what he had to say about aromatase inhibitors. 

As to whether it was "misleading" to post the link to Dr. Winer's video here, .... I would prefer to leave that up to the women who frequent this forum. 

Yazmin has been a member of BCO a lot longer than most of the rest of us, and she apparently thought it was okay to put the link here.  The point Dr. Winer made about Arimidex providing no statistically significant improvement in survival is something all of us with ER+ tumors need to realize.  My goal in adding the transcript was to make sure everybody understood that Dr. Winer was referring to studies in which Armidex was compared to tamoxifen or to sequential tamoxifen/Arimidex combinations, and not to placebo.

vivre offered some personal comments about studies on Arimidex, telling us what bothers her about the design of those trials (i.e., the fact that Arimidex has only been compared with other drugs).  She suggested that a comparison between Arimidex and a more "natural" strategy for decreasing estrogen levels would be welcome.  I agree completely, although I get all muddled when I try to figure out how those studies would be designed.  The participants would need to be able to volunteer for the test group they would be in, since random assignment would likely be considered unethical.  And, it would be difficult to use a "blinded" design in which nobody knew which treatment they were getting.  I'm pretty sure I would figure it out if I suddenly discovered I was spending a lot more time on my elliptical machine.

I am enjoying the relatively mild-mannered give-and-take on this thread.  (Everything is relative.  I was involved in some threads that got so hot they imploded last week.)  Some questions have been asked here (e.g., Arimidex dosing based on weight, etc.) that need answering, or at least need discussing.  I have some ideas about how the powers decided 1 mg was the right dose, and I even have some evidence (journal articles from the 1990's).  But I haven't put the words together into a coherent response yet.  I'm not even sure Yazmin wants this thread to head that direction.

otter

[Edited: After re-reading my post, I realized I had erred in saying it was Yazmin who had claimed there was no survival benefit with Arimidex.  She did not make that statement, at least not in this thread.  That is something Dr. Winer said in the video, however; so I've edited my post accordingly.]

Lowrider54

This was posted by kira and I think it is of interest here.  When one is quoting 'undisputable facts' from scientific studies - that may not always be the case:

There was a great New Yorker article: The Truth Wears Off, about the fact that much scientific research is not able to be replicated and bias is inherent, and the general limitations of scientific studies.

Now we depend on these studies in our situation, but we also have seen pendulums swing, and previously held scientifc truths both be debunked and re-adopted (last week's NE Journal showed that antibiotics actually help ear infections, while the knowledge of the last few years was that they should not be used.)

So, here's a link to the article

http://www.newyorker.com/reporting/2010/12/13/101213fa_fact_lehrer#ixzz1AIkDhn6D

A couple of quotes stood out for me:

Before the effectiveness of a drug can be confirmed, it must be tested and tested again. Different scientists in different labs need to repeat the protocols and publish their results. The test of replicability, as it's known, is the foundation of modern research. Replicability is how the community enforces itself. It's a safeguard for the creep of subjectivity. Most of the time, scientists know what results they want, and that can influence the results they get. The premise of replicability is that the scientific community can correct for these flaws.

But now all sorts of well-established, multiply confirmed findings have started to look increasingly uncertain. It's as if our facts were losing their truth: claims that have been enshrined in textbooks are suddenly unprovable. This phenomenon doesn't yet have an official name, but it's occurring across a wide range of fields, from psychology to ecology. In the field of medicine, the phenomenon seems extremely widespread

...........

According to Ioannidis, the main problem is that too many researchers engage in what he calls "significance chasing," or finding ways to interpret the data so that it passes the statistical test of significance-the ninety-five-per-cent boundary invented by Ronald Fisher. "The scientists are so eager to pass this magical test that they start playing around with the numbers, trying to find anything that seems worthy," Ioannidis says. In recent years, Ioannidis has become increasingly blunt about the pervasiveness of the problem. One of his most cited papers has a deliberately provocative title: "Why Most Published Research Findings Are False."

The problem of selective reporting is rooted in a fundamental cognitive flaw, which is that we like proving ourselves right and hate being wrong. "It feels good to validate a hypothesis," Ioannidis said. "It feels even better when you've got a financial interest in the idea or your career depends upon it. And that's why, even after a claim has been systematically disproven"-he cites, for instance, the early work on hormone replacement therapy, or claims involving various vitamins-"you still see some stubborn researchers citing the first few studies that show a strong effect. They really want to believe that it's true."

That's why Schooler argues that scientists need to become more rigorous about data collection before they publish. "We're wasting too much time chasing after bad studies and underpowered experiments," he says.

...........Such anomalies demonstrate the slipperiness of empiricism. Although many scientific ideas generate conflicting results and suffer from falling effect sizes, they continue to get cited in the textbooks and drive standard medical practice. Why? Because these ideas seem true. Because they make sense. Because we can't bear to let them go. And this is why the decline effect is so troubling. Not because it reveals the human fallibility of science, in which data are tweaked and beliefs shape perceptions. (Such shortcomings aren't surprising, at least for scientists.) And not because it reveals that many of our most exciting theories are fleeting fads and will soon be rejected. (That idea has been around since Thomas Kuhn.) The decline effect is troubling because it reminds us how difficult it is to prove anything. We like to pretend that our experiments define the truth for us. But that's often not the case. Just because an idea is true doesn't mean it can be proved. And just because an idea can be proved doesn't mean it's true. When the experiments are done, we still have to choose what to believe. ♦

Just putting this out there as another example of why scientific studies are so important to us, and why the data keeps shifting and the inherent problems with research.

Member_of_the_Club

I read the New Yorker article when it came out and it is a cautionary tale, though I sure prefer studies and results over nothing.  I don't think anyone objects to Yazmin posting the link.  I have certainly heard of Dr. Winer and was interested.  And I think it is news to a lot of people that AIs are pretty as effective as tamoxifen.  I was surprised when my onc told me that because AIs have been touted as better and more effective, and there is a lot of pressure on women to switch to them from tamoxifen, so I think this is an important message.  Post-menopausal women who have trouble with AIs should have no reluctance at all about switching to tamoxifen.

Husband11

ivorymom,

 I think its important to distinquish between the observation that for a population of women in a study, AI's offered similar survival advantage to tamoxifen, and any conclusion that for an individual, their results on tamoxifen would have any bearing on the effectiveness of an AI.  Lowrider 54's experience bears this out.  The ability of an individual to choose among the various hormonal therapies is certainly valuable.

lago

I think my onc prefers Als to tamox because of the risk of endometrial cancer (although very small) and some of the other SEs that can be more serious (blood clots). There is the risk of osteoporosis (real risk for my with osteopenia, my mom's history, I'm thin, small bones, white used to smoke etc.) but we are watching this. I will be getting another bone density test in a year to see if things are getting worse.

In many articles they have thought that Als were slightly better than tamoxefin. This video now questions that… granted the increase was very slight so no big surprise here.

Lowrider54

Hi Member - I can say that the Al's ARE much more effective in the first line treatment of mets - and I think they were hoping it would be in the prevention as well and it didn't turn out to be the case - but they are just as effective which does gives those with Tamoxifin issues an option.  And it does show that, like you said, post-menopausal women can use them interchangeably. 

And true - studies are better than nothing but to be viewed with caution and not taken as 'undisputable facts' - I don't think there are any 'undisputable facts' in this crazy world of bc - just best educated determinations based on the individual.

pj12

Thanks to Yasmin and everyone here for starting this thread and discussing all the pros and cons. As a person who had to stop anastrazole after 15 months and switch to Tamoxifen it is reassuring and comforting to think I have not ruined all chance of living a long healthy life. 

I think it is important to recognize we are all trying to do the best given our individual circumstances. What has turned out necessary and hopefully right for me is my journey and I can tell everyone else how and why but I can't imagine being angry that someone chooses her own path. 

Wishing every one of us success.

Pam 

Kathy044

JMO, but I happen to think keeping these negative posts here out in the open where others can respond to them serves a better purpose than trying to ignore or eliminate them. I don't know about others here, but each time I read them I go back again and look at the evidence myself. 

For anyone interested in more up to date information than that mentioned in the original post, the editorial comment Michael Gnant wrote to accompany the ATAC 10 year results on The Lancet Oncology in December 2010 is freely available if registered with the site. (anyone can register, it easy to do).

http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2810%2970270-9/fulltext

10 years of ATAC: one question answered, many others unresolved

Btw, if we want to be picky, 10 years out Armidex did have a slight overall survival advantage over Tamoxifen, and an even better disease free survival advantage over the same.

Heidihill

After I found out I was an ultra rapid metabolizer of Tamoxifen, it got me thinking that all these expensive studies are probably a waste and personalized medicine still has a way to go. We don't know, for example, if the Tamoxifen arm would have been mostly normal metabolizers or poor metabolizers. If they were mostly poor metabolizers, than this certainly would skew the results. Unless they think the metabolism issues in both arms would somehow be equal. Who knows?

Member_of_the_Club

The metabolizing test has been found on further study to not mean much, so I think we will be hearing less and less about it.

kira66715

Dr. Winer works at DFCI and this interview is now 2 years old: I just looked at the 2010 ASCO guidelines, co-authored by Harold Burstein at DFCI, a colleague of Dr. Winer, nothing really new, but it spells out the issues of tamoxifen vs. AI:

This is a free full article

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2936467/?tool=pubmed

This comment struck me:

In absolute terms, the reduction in risk of recurrence associated with AI-based therapy compared with tamoxifen is modest, typically amounting to less than 5% through multiple years of follow-up. However, studies consistently report improvements in disease-free survival. Inclusion of an AI is recommended because locoregional recurrence, contralateral breast cancer, and earlier distant metastatic recurrence are clinically important to patients. 

As someone who might possibly fall into the "extended" group, and who sees Dr. Burstein as a patient, I've noticed that his opinion has been changing, and he's waiting for "safety studies" as of our last visit.

Kira

Janeluvsdogs

Kira, thanks so much for citing the most recent information in the guidelines.

pj12

Kira,

Thank you for the updated information. And please keep us informed as Dr. Burstein's opinion evolves.

Pam 

wallycat

Someone on the ILC board posted a link to an article published on breastcancer.org that

some (and I don't know how you tell if you are in the group or not) lobular cancer does not benefit from tamoxifen.  Maybe the AIs showing improvement are leaning towards that group?

I am ILC and just started arimidex but I am nervous about the cardiac problems mentioned at the symposium....I guess we pick our demons, huh?

Anonymous

1. Yes, Dr. Winer prescribes both tamoxifen and all the Ai's.  Yes, they do show a marked decrease of reoccurance, as he states in the very beginning of this video ( 2009) - and he compares the two.

There has not been, as he goes on to state, enough data to show statistical significance in survival rates.  Lowrider went into great detail earlier in this thread to explain that - thank you Lowrider, for all the new people who may be reading this thread.

Some people seem to have a distinct interest in trying to make the Ai's look "bad" - and target that "red herring" about "survival rates."  I don't understand that agenda and  hope all the women reading this will concentrate on Lowrider's informative comments, and work with their respsective doctors to find a treatment plan which is best for them.

Interesting, there is not a "competition" between "natural" and "western medicine" at DFCI.  They have an excellent Complementary Care Center - and urge any woman who wants to, to make appointments for treatments: acupuncture, massage, and nutritional counseling.  I wish every woman had a doctor as concerned as Dr. Winer is about the QOL ( quality of life) of his patients, as a vital part of each treatment plan.

JSwan

All I can say is that my large ILC tumor has shrunk considerably after being on neoadjuvant anastrozole for five months.  I will live with the night sweats and joint pain.

KatesParelliMom

Hello, board! New member posting here. I've been a visitor many times and have learned that so many of you know a lot about bc meds and treatment and I simply can't wrap my mind around it all. Any advice would be appreciated . . . I am 47 years old, 45 when diagnosed; chemo threw me into menopause -- no period since August '08. Began Tamoxifen Oct. 1, 08. After two blood tests (Oct and Dec. '10), onc concluded that I am post-menopausal and said it was time to go on an AI and gave me Femara. And prescribed Boniva since I have osteopenia. Come to find out that bisphosphonates can have serious side effects (like disfiguring jaw bone damage). My husband is none too pleased about the potential skeletal injuries that go along with Femara and then Boniva, et all, create another set of worries. He wants me to go back on Tamoxifen. I did start Femara but not Boniva -- the onc will evaluate me at the end of Feb. to see how I'm doing. 

How do I decide if staying on Tamoxifen is better? Or if moving to the AI is? And why is this decision harder than deciding to do chemo? Or have reconstructive surgery (that was actually a no-brainer for me)? After not having to make "big" decisions (mastectomy, chemo, etc.) for a couple of years, it's really messing with me. How have you all coped with the ongoing nature of bc treatment? Anyone with a magic wand who wants to wave the answers in my direction?  Thanks for letting me share . . .  

 

Anonymous

KatesPareliMom

I think you will get more information if you post on threads in the forum Hormonal Therapy.  There are several threads there addressing the questions you are asking.  As you are a new member of BC.org, you will be limited to 5 posts a day until you reach 50 posts.  This "Alternative" thread is not focused on Hormanals as the other Forum is.

JSwan - you too will find excellent advice in the Hormonals Forum on "AI SE's" ( side effects).  ost of us have experienced some joint pain, hot flashes, and using all the suggestions from each other have really just about eliminated all of them!  Good luck.  You will find great information on threads in the Hormal Forum - especially those started by LowRider!

lago

KatesParelliMom How bad was your osteopenia. I have it but my onc left the decision up to my regular internist regarding a bisphosphonate . Internist said mine was so slight that he is not recommending this at this time. We will do another bone scan in a year because I am going on Anastrozole, as well as have a history (mom had osteperosis), think, white etc.

otter

Thanks, Kira, for the update.  I appreciate the link to the newest ASCO guidelines.  Somehow I had missed that. Burstein and Winer have been sources of info on the aromatase inhibitors for many years. I do have one question, though (more of a reqest for clarification), and one comment/correction.

First, the request for clarification:  was the 5% the "absolute" reduction in risk, or a "relative" reduction?

The lines quoted from the ASCO paper included this:  "In absolute terms, the reduction in risk of recurrence associated with AI-based therapy compared with tamoxifen is modest, typically amounting to less than 5% through multiple years of follow-up."  I assuming the authors were talking about the absolute decrease in recurrence risk ("in absolute terms") when Arimidex was compared to tamoxifen. But I don't know that for sure.

There has been a lot of discussion on these boards about "absolute" versus "relative" benefits of a particular treatment, and the importance of knowing which we're talking about.  If the 5% decrease in risk was a relative decrease, then the benefit of Arimidex would, indeed, be trivial (IMHO).  As an example, let's say (hypothetically) that women on tamoxifen saw a 40% lower risk of recurrence over the observation period, than women who were taking a placebo.  (That's a hypothetical number, okay?)  If the 5% improvement with Arimidex was the relative benefit, then the women taking Arimidex would see (on average) a 42% decrease in their recurrence risk (40% + [0.05 x 40%] = 42%).  That's a downright puny gain over tamoxifen.  I thought the benefits in recurrence risk for Arimidex over tamoxifen were better than that.

OTOH, if the 5% improvement with Arimidex was the absolute benefit compared with tamoxifen, that would mean the women taking Arimidex would see (on average) a 45% decrease in their recurrence risk (40% + 5% = 45%).  I would not have characterized that as a "modest" benefit.  I would be happy with that gain; it would motivate me to choose Arimidex rather than tamoxifen (which it did).

Okay, then my comment/correction (and please don't get mad at me)....  I don't think the video Yazmin posted is 2 years old.  That interview is more like one year old (perhaps a bit over 13 months).  The video was produced in conjunction with the 2009 San Antonio Breast Conference Symposium, which was held in December 2009.  Curetoday published some press releases and summaries from the 2009 symposium, the video being among them.  Here's a link to the Curetoday page where the AI findings are discussed and a link to the video of Winer's interview is provided: http://www.curetoday.com/index.cfm/fuseaction/article.show/id/2/article_id/1324

I couldn't find a date on that page, but the introductory line on the Youtube page at Yazmin's link says:

curetoday  |   March 03, 2010  |  0 likes, 1 dislikes
Editor-in-chief, Debu Tripathy, MD, and Dana-Farber's Eric Winer, MD, discuss where we stand on hormonal therapy at the 2009 San Antonio Breast Cancer Symposium.

So, it looks like Curetoday might have posted the video on Youtube less than a year ago.  It's true that the data from the clinical trials reported at the 2009 meeting could have been nearing their first birthday by then (which is typical of results presented at major professional meetings).  So, the results to which Dr. Winer referred in the video might  be 2 years old by now.  And, I do think we need to be looking at the most recent results (and opinions) available.

...but even if his statements are outdated, I still liked being able to watch Dr. Winer say those things in his own words; and I was glad the video was high-enough quality that I could transcribe it.

otter

Anonymous

JSwan

If you have questions of any of the posts you find on the Hormonal Threads about dealing with side effects - you can also PM ( send a Private Message) the person and ask for information - as you are limited to 5 posts a day for now.   You click on the member's name on the left of the post you have a question about- and it takes you to that member's Home Page - click on Send a Private Message.

You will find the "answer" on your own Home Page - in the upper right hand corner. You'll find very valuable information on dealing with side effects ( SE's) on the thread started by LowRider.

mathteacher

Otter, just by looking at the single digit figure you can assume it is an absolute risk figure. All the adjuvants seem to line up in the single digits for absolute risk. Relative risk for Tamoxifen is usually given as 50%. Dr. Winer is scrupulous in not using the misleading relative risk figure. Some doctors are not so forthcoming.

The new strategy seems to be to gather multiple, small statistical victories to accrue better survival. Personalized medicine may be harder to measure if we are targeting different pathways.

molly52

Hi Sherri,

Beyond 5 years, it's a cr@p shoot.  From what I can see, the "experts" say no more than 5 years total (Tax + AIs).  However, a number of oncs are going past the 5 years.   As far as I know, there is no science to prove a benefit.   But if you must, then a break (2-3 yrs?) before continuing.

Tamoxifen (I believe) ran into a problem when taken over 5 years.  Pretty sketchy on what the problem was, perhaps, aggressive cancer in the opposite breast????  I didn't take Tamoxifen, so did not really pay attention.

You could ask your onc what study supports his/her decision, or what is the basis of the decision.  Also, you could try some of the "natural girls" methods to lower estrogen.

I have finished my five years but am still waiting for the side effects to wash out of my system.  Then I will start some sort of natural protocol (tbd).

I haven't had my estradiol measured, so I have an advantage over you.  I don't know if it is high - so I can live in de nile. (LOL).

You've got a tough decision to make.  Good luck.

PS, I am not an expert.  Others may give you better advice.

Lowrider54

Sherri...just an FYI...ONLY Tamoxifin for longer than 5 years can present an issue - it has been a long time since I looked at it but I will try to dig it up over the weekend for you.  I had to stop after 2 1/2 years due to a lesion on my cervix removed at age 22 - I was 44 when the bc presented and 45 by the time I was taking the Tamoxifin - with the study about the increased risk of ovarian cancer and maybe cervical cancer - I was taken off of it.  I did not go to an Al.

Now with mets - Tamoxifin is again an option - I am way post menopausal but it is an AL of sorts as is suppresses estrogen so it is in the arsenal for me with mets. 

I would look at things this way - if Al's can be taken for long periods to knock back mets - I mean years and years - then I would have to conclude that there is not an issue taking any of them of long periods - with the exception of Tamoxifin.  If you are not having a recurrence then it is doing its job!  That is the goal, prevention of recurrence and if you are living a cancer-free life - honestly, you are most definately doing something very right!  And in your situation - I would keep doing it and not give it another thought.

Just my opinion...hugs to you and may you NEVER see the beast again!

LowRider

lago

As mentioned earlier one of the problem with Als is osteoporosis. If you have an issue/history then this can be a problem especially if you take them for more than 5 years. Bisphosphonates can help with osteoporosis but they too have issues/SE especially if you are on them for a long time. Granted I would rather risk/treat osteoporosis than cancer. Osteoporosis can be reversed in some women… cancer there is no redos

imbell

Cynical me says I paid the drug company $3276 over 18 months and then had a recurrence on Arimidex. I then got Aromasin for about 6 weeks. Same drug, same outcome. I then had chemo and was put on Tamoxifen. Why? I am 67. My answer is, it is cheap, at $20/month so no one has to feel guilty about the cost as it probably won't work. As Dr. Winer says, it is for prevention not cure. Is it worth the side effects. Don't know as my side effects are extreme heartburn and chest pain not hot flashes. There have been women on Tamoxifen for 5 years that had no recurrence. Was it the Tamoxifen? Does age make a difference. P.S. Tamoxifen is hard on the liver.

KatesParelliMom

Wow. Sorry, Caerus, for burdening the thread. It won't happen again.

Member_of_the_Club

The five year limit on tamoxifen is because the risk of endometrial cancer goes up after that and the effectiveness goes down.  However, i know a woman with mets who was on tamoxifen for 10 years because it kept her stable.  Since she had mets, they could see that it was working and the benefits far outweighed the risk of endometrial cancer.  Tamoxifen can be a very powerful drug.